| Diabetes can involve the whole vessel system, the involved organs of patients with diabetes have general pathological changes. The microvascular pathological changes especially retina changing are mainly chronic complication of diabetes, its serious degrees has close relation to surviving rate of patients with diabetes. Hence, serious degrees of eye pathological change represent development of pathological changes of all the vessel.The latest researches shows that pericytes of retina and retinal pigment epithelial , play key pathologic role in diabetic retinopathy both morbidity and consequence. Therefore we chose the two cytopathy models to screen drugs.In the first part of thesis, we screened the herbs through the effect of the proliferation of pericyte and RPE .The herbs such as puerariae,rhizoma pivrorhizae, anamarrhenae and so on have been turned out to the effective herbs the inhibition or encourage the proliferation.In the second part, the compound formula of TCM, CFH206 has been made up according to the effect that screened via pericyte and RPE cytopathy model and the theory of TCM. Then researched the effect of CFH206 on the proliferation of pericyte, RPE, gelical cells, macrophage , the cells in retina induced by glucose , AGEs, and the effect on nonenzymatic glycation of protein.The result indicated that CFH206 had remarkble protective effect on inhibitory proliferation of pericyte in high glucose andsignificantly inhibited proliferation of RPE and the cells of retina induced by high glucose. Futher CFH206 have protective effect on injury of pericyte , macrophage and gelical cells induced by AGEs. Additional, CFH206 had inhibitory effect on formation of AGEs . These results indicated that CFH206 has effect of retarding incidence and development of DR.In order to verify the effect in vitro and the effect of the CFH206 , which had been produced by the cytopathy model, CFH206 was tested by pharmacological in vivo . The diabetic animal model induced by STZ-CFA plus 30% protein diet had been used that improved by us. In the first section , we observe the effect of CFH206 on postprandial blood glucose level, body weight, food and water intake, percentage of cataract . The results show that CFH206 can decrease food and water intake , urinary albumin and urine volume. In the second section , we observe the effect of CFH206 on biochemical parameter such as the AGEs , NO in retina, lens, sciatic nerve , renal and the MDA, LDH, SOD, GSH-Px in the serum of diabetic rats induced by STZ-CFA. The results show that CFH206 can increase the serum SOD, GSH-Px , decrease the serum MDA, LDH and the concentration of AGEs, NO in lens, sciatic nerve and retina. In the third section , the morphological pathology have been used to observed the changes of pancreas, kidney and retina. We found CFH206 decrease the ratio of E/C(endothelium / pericyte ) and the percentage of microvascular in retina , protect the retina from injury , it decrease the mesangium area also . The morphology of retina, pancreas, kidney , lens of animal modelchange greatly, and the CFH206 can alleviate these changes except the insulitis.These results show that both the proliferation of pericyte and RPE induced by high glucose and AGEs in vitro are the correct model for diabetic drug screening. The STZ-CFA induced rat diabetic model is suitable for the testify the drug for antimicroangiopathy medicine screen.We believe that the research and development of TCM in nowadays should via the probe both in vitro and in vivo. We also believe that the TCM , the richest treasure of Chinese medicine culture are the foundation of diabetic microangiopathy research , while we need modern idea theory and technology for the research , so as to make TCM modernization.
|
PDF Full Text Request